Which molecule acts as transcriptional coactivator that promotes mitochondrial biogenesis in skeletal muscle following endurance training?

• A. NF-κB
• B. AMPK
• C. PGC-1a
• D. mTOR

Answer: (C)

Endurance training boosts mitochondrial biogenesis by activating a transcriptional coactivator that links energy sensing to the mitochondrial gene program. This molecule is PGC-1α. It doesn’t bind DNA on its own; instead, it coactivates transcription factors such as NRF-1 and NRF-2 to drive the expression of nuclear-encoded mitochondrial genes and support mitochondrial DNA replication via factors like Tfam. As a result, mitochondrial content and oxidative capacity in skeletal muscle rise, supporting improved endurance performance. Exercise triggers PGC-1α activation through pathways such as AMPK and p38 MAPK in response to energy stress and calcium signaling. The other options don’t fit this role: NF-κB is mainly involved in inflammatory responses, AMPK is an energy-sensing kinase that activates PGC-1α but is not the coactivator itself, and mTOR promotes growth and protein synthesis rather than mitochondrial biogenesis.